All visual information is conveyed to the cortex via geniculocortical (GC) synapses, yet how GC inputs drive intracortical interactions is only poorly understood. The common view is that visual activation, initiated in the retina, is relayed through the lateral geniculate nucleus (LGN) to layer 4 (L4) neurons. Activity then flows through the cortex from L4 to layer 2/3 (L2/3), then layer 5 (L5) followed by layer 6 (L6). However, several lines of evidence suggest that this description is grossly simplified. First, while anatomical studies show that GC axons primarily innervate L4 and lower L3, additional GC terminals target L6 and L1. Although the innervation of L6 and L1 is relatively modest anatomically, the functional impact of these synaptic inputs may be significant. Thalamic input will drive these different layers in parallel, and its impact will depend on intracortical interactions among the thalamorecipient cells. Second, the synaptic strength and dynamics of GC synapses may play an important role in shaping the transmission of visual information to the cortex. Whether geniculocortical synapses are exceptionally efficacious and reliable is controversial. Different classes of geniculate relay neurons may exhibit distinct synaptic properties, but this has not been explored. Furthermore, GC inputs target different classes of excitatory and inhibitory neurons, and the identity of the cortical postsynaptic targets may also influence the functional properties of GC synapses. Diversity in the synaptic properties of GC synapses could change the balance of excitation and inhibition during ongoing GC activity, profoundly affecting cortical processing of visual information. To address these issues, we will selectively express a light-gated cation channel, channelrhodopsin-2 (ChR2), in GC neurons to optically stimulate GC fibers in isolation. Combined with our extensive experience in targeted recording from different classes of inhibitory and excitatory neurons in visual cortex, this novel approach will allow us to develop a comprehensive view of how different GC inputs drive cortical circuits during ongoing visual stimulation. PUBLIC HEALTH RELEVANCE: The proposed experiments will uncover mechanisms that underlie the flow of visual information through the brain. Understanding these mechanisms will further our understanding of normal brain function and facilitate the diagnosis and treatment of neurological and psychiatric disorders.